A Case of Necrotizing Pneumonia Caused by Co-Infection With

Apr. 2018 THE JAPANESE JOURNAL OF ANTIBIOTICS 71―2 71（ 21 ）〈Case Report〉 A case of necrotizing pneumonia caused by co-infection with inuenza B and a Panton–Valentine leucocidin negative community acquired methicillin–resistant Staphylococcus aureus strain Keiji Mouri1, Yoshihiro Kobashi1, *, Shigeki Kato1, Tetsuo Yamaguchi2 and Mikio Oka1 1 Department of Respiratory Medicine, Kawasaki Medical School 2 Department of Microbiology and Infectious Diseases, Toho University School of Medicine (Received for publication January 25, 2018) A 63-year-old woman visited our hospital complaining of fever and dyspnea. Her inflammatory response was strongly positive, with hyperglycemia, severe hypoxia, a high level of procalcitonin, and an influenza B antigen-positive result. Chest computed tomography (CT) on admission showed multiple nodules with infiltrative shadows in the bilateral lung fields, and gram-positive coccus with phagocytosis by neutrophils was observed in a sputum sample. Although treatments using sulbactam/ ampicillin (SBT/ABPC) and azithromycin (AZM) plus peramivir were initiated, the clinical effect was poor due to the delay of administration of linezolid (LZD). Because methicillin-resistant Staphylococcus aureus (MRSA) was isolated from sputum, treatments were changed to LZD plus AZM. Molecular analysis of the MRSA isolate showed as follows: multilocus sequence typing (MLST) 8, staphylococcal cassette chromosome mec (SCCmec) typeIV, spa type t1767, Panton- Valentine leucocidin (PVL)-negative, arginine catabolic mobile element (ACME)- negative, and toxic shock syndrome toxin-1 (TSST)-1-positive. Influenza B and TSST-1 produced by community acquired MRSA (CA-MRSA) may have been involved in the formation of necrotizing pneumonia in this patient. However, she improved following the administration of peramivir and LZD. *Correspondence to Yoshihiro Kobashi, Department of Respiratory Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701–0192, Japan Tel.: ＋81–86–462–1111, Fax: ＋81–86–464–1041, E-mail: [email protected] 72（ 22 ） THE JAPANESE JOURNAL OF ANTIBIOTICS 71―2 Apr. 2018 Introduction Methicillin-resistant Staphylococcus aureus (MRSA), which has the staphylococcal cassette chromosome mec (SCCmec), has been a known nosocomial pathogen since 19611). Another class of MRSA, known as community-acquired MRSA (CA-MRSA), first emerged in the community from 1997 to 1999, and has since become a major concern worldwide2). CA-MRSA is mainly associated with skin and soft tissue infections, but sometimes with unusual and severe infections such as bacte- remia, sepsis, and necrotizing pneumonia in healthy individuals without risk factors2, 3). CA-MRSA has type IV or V SCCmec, which exhibits low minimum inhibitory concentration (MIC) values for oxacillin or imipenem, is resistant to β-lactam agents only, and often produces Panton-Valentine leucocidin (PVL), a toxin acting against polymorphonuclear neutrophils and monocytes2) in western countries. The PVL-positive sequence type (ST) 8/SCCmecIV MRSA in the United States (USA300) is one of the most common and best characterized forms of CA- MRSA4). USA300 carries the arginine catabolic mobile element (ACME), which is considered to promote the colonization and survival of USA3004). In Japan, most CA-MRSA consists of ST8 CA-MRSA, which is negative for PVL and ACME5–7). We report a rare case of necrotizing pneumonia due to co-infection of influenza B and CA-MRSA, showing negative responses for PVL and ACME, but a positive response for toxic shock syndrome toxin-1 (TSST-1). Case Report A 63-year-old woman with diabetes mellitus (receiving no medication) was admitted to our hospital complaining of fever and dyspnea that had started three days earlier (April 1, 2014). She had a smoking history (30 cigarettes per day for 40 years), but there were no other potentially contributing factors excluding diabetes mellitus. She was not received influenza vaccine inocula- tion in 2013–2014. She had never been abroad. Her consciousness level was 1 on the Japan Coma Scale (14 on the Glasgow Coma Scale) on arrival and her vital signs were as follows: blood pres- sure 150/76 mmHg, pulse 130/min (regular), respiratory rate 30/min, oxygen saturation 95% (O2 5 L mask), body temperature 38.6°C. On physical examinations, coarse crackles and rhonchi were auscultated in both lung fields. Laboratory examinations on admission are shown in Table 1. In- flammatory response including WBC and CRP were markedly elevated. Glucose and HbA1c, re- lated to diabetes mellitus, were also markedly elevated. Mild liver dysfunction was also recognized. Arterial blood showed respiratory and metabolic acidosis, elevation of AaDO2, and degradation of PaO2/FIO2. Concerning serological examinations, elevation of procalcitonin and a positive response to influenza B antigens were noted. Although the blood cultures for common bacteria, urinary pneumococcal antigens, and urinary legionella antigens were negative, Gram Apr. 2018 THE JAPANESE JOURNAL OF ANTIBIOTICS 71―2 73（ 23 ） Laboratory examination data on admission Table 1. Table 74（ 24 ） THE JAPANESE JOURNAL OF ANTIBIOTICS 71―2 Apr. 2018 Fig. 1. Chest radiograph on admission showing infiltration shadows in the right middle and left middle and lower lung fields staining of purulent sputum (Miller-Jones classification: P3) revealed many inflammatory cells phagocytizing gram-positive coccus bacilli. Regarding the radiological findings on admission, infiltrative shadows appeared in the right middle and left middle and lower lung fields on chest radiograph (Figure 1). Infiltrative shadows and centrilobular nodular shadows were recognized in the right upper and lower lobes and left upper and lower lobes on chest computed tomography (CT) (Figure 2). We showed the clinical course of this case in Figure 3. Although antibiotic therapy using sulbactam/ampicillin (SBT/ABPC), azithromycin (AZM) and peramivir was immediately initiated after admission, respiratory failure advanced and necessitated mechanical ventilation support on day 1. From the sputum culture on admission and aspiration sputum culture of a bronchoscopic specimen, MRSA was detected. The antimicrobial susceptibility of the isolated MRSA is shown in Table 2. Under the diagnosis of CA-MRSA pneumonia according to the definition described by Naimi et al.8), the antibiotic therapy was changed to combination therapy consisting of Linezolid (LZD) and AZM on day 6. Although the respiratory condition gradually improved, several cavi- tary lesions appeared in both lungs with atelectasis of the left lower lobe on chest CT on day 10 (Figure 4). We considered that the pneumonia due to CA-MRSA had deteriorated to a pulmonary abscess due to the delay of administration of LZD. However, because Pseudomonas aeruginosa and Klebsiella pneumoniae were newly detected from the sputum culture, tazobactam/piperacillin (TAZ/PIPC) was added as antibiotic therapy. The clinical course of this patient gradually improved, and she was discharged on day 22. Whole-genome sequencing of the MRSA isolate (strain TUM 14604) was carried out by Apr. 2018 THE JAPANESE JOURNAL OF ANTIBIOTICS 71―2 75（ 25 ） Fig. 2. Chest CT on admission showing infiltrative shadows and centrilobular shadows in the right lower lobes and left upper and lower lobes Fig. 3. The clinical course of this case showing with drugs for treatment, the transitional change of respiratory conditions and inflammatory responses 76（ 26 ） THE JAPANESE JOURNAL OF ANTIBIOTICS 71―2 Apr. 2018 Table 2. Antimicrobial susceptibility of isolated MRSA next-generation sequencing using MiSeq (Illumina, San Diego, CA, USA). The draft genome sequence data were assembled using CLC Genomics Workbench v 9.5.1 software (Qiagen, Aarhus, Denmark). Multilocus sequence typing (MLST) was performed using 7 housekeeping genes, and an allelic profile was obtained from the MLST website (http://www.mlst.net/). SCCmectype and spa type were determined, and the presence of virulence genes was checked. The sequence type was ST 8/SCCmec typeIV, and the spa type was t1767. The results for virulence genes were as follows: PVL (lukSF-pv)-negative, ACME (arcA)-negative, exfoliative toxin (ET)(eta, etb)-negative, and TSST-1 (tst-1)-positive. Discussion We encountered a patient with diabetes mellitus without medication who showed necrotizing pneumonia caused by co-infection with influenza B and PVL-negative CA-MRSA. Although there was a report that the frequency of MRSA increased among elderly patients with community-acquired pneumonia (CAP)9), there are few reports concerning necrotizing pneumonia due to co-infection with influenza B and CA-MRSA in Japan. Apr. 2018 THE JAPANESE JOURNAL OF ANTIBIOTICS 71―2 77（ 27 ） Fig. 4. Chest CT on day 10 admission showing several newly observed cavity lesions in both lungs with atelectasis of the left lower lobe CA-MRSA corresponds to MRSA infection occurring in patients without risk factors for MRSA infection, such as a past history of admission to a hospital or nursing home, surgery, hemodialysis, and use of an intravenous reservoir8, 10). Naimi et al. defined CA-MRSA as satisfying the following criteria: (1) the detection of MRSA in clinical specimens obtained from an outpa- tient or inpatient within 48 hours after admission with infectious signs, (2) no past history of MRSA detection in clinical specimen cultures, (3) no past history of admission to a hospital or nursing home within the last one year, surgical operation, or hemodialysis, and (4) no use of a reservoir such as an intravenous

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